Retinoids are a class of naturally occurring and synthetic derivatives of Vitamin A which function in vivo as regulators of a number of physiological functions including cellular proliferation, cytodifferentiation and embryonal morphogenesis. This class includes a number of clinically important compounds such as those shown FIG. 1 which have been shown or hypothesized to have utility in the therapy and prevention of various types of cancer. For example, Hong et al., N. Eng. J. Med. 323: 795-801 (1990) have shown that adjuvant treatment with 13-cis retinoic acid after definitive anti-cancer treatment in patients with carcinoma of the head and neck significantly reduces the incidence of secondary tumors of the aerodigestive tract. Head and neck cancer, like lung cancer, is significantly related to tobacco smoking, and in fact many of the tumors reduced in incidence in the Hong et al. study were lung cancers. Retinoids have also been shown to be effective in the prevention and reversal of certain types of induced hyperplasia and metaplasia in cultured rodent respiratory epithelia. Lasnitzki et al., Cancer Treatment Reports 66: 1375-1380 (1982).
Unfortunately, while retinoids have been shown to provide beneficial effects in the prevention of at least some types of cancer, the therapeutic regiment requires chronic administration. Under these circumstances, substantial systemic toxicity may result, including hyperlipidemia, hypercalcemia, and skin, liver and central nervous system toxicity. This toxicity has limited the utility of retinoids as therapeutic agents in the prevention of cancer.